POEMS sindrome: role of two angiogenic factors, VEGF and EPO

POEMS syndrome is a rare disorder characterized by the combination of polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes. The pathogenesis of this multisystemic disease is not known. Recently, an association with high levels of serum VEGF (vascular endothelial growth factor), a multifunctional cytokine that induces angiogenesis and microvascular hyperpermeability, has been reported. Both VEGF and erythropoietin (EPO), an acidic glycoprotein hormone that also promotes endothelial proliferation, are under the control of a transcription factor called hypoxia-inducible factor (HIF). To determine whether these angiogenic factors may have a pathogenic role in POEMS, we longitudinally evaluated VEGF and EPO serum concentrations by ELISA in ten patients during the clinical course and in relation to the therapy response. All patients had initially high levels of VEGF and low EPO concentration and there was an inverse correlation between VEGF and EPO levels during the disease progression. We have also analyzed sural nerve biopsies of seven POEMS patients. The presence of VEGF/VEGF-R and EPO/EPO-R immunostaining in the endoneurial and perineurial vessels has been shown, as well as in some of the non-myelin forming Schwann cells identified as glial fibrillary acidic protein (GFAP) positive cells.